Survival outcomes for patients (pts) with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with lutetium-177-dotatate (Lu-177) in a Brazilian reference center: A six-year follow-up experience.
Authors: Zenaide Silva Souza, Camila Bragança Xavier, Luciana Beatriz Mendes Gomes Siqueira, Maria Fernanda Barbosa de Medeiros, Micelange Carvalho de Souza, Maria Dirlei de Souza Begnami, Allan Andresson Lima Pereira, José Flávio Gomes Marin, Carlos Alberto Buchpiguel, Frederico Costa
Journal: Journal of Clinical Oncology (2023)

642 Background: GEP-NETs are the most common NETs primary site. Lu-177 is the standard treatment for patients with grade 1 (G1) or grade 2 (G2) midgut NETs who had disease progression during first-line somatostatin analog therapy. Methods: We performed a retrospective chart review including advanced GEP-NETs treated with at least one Lu-177 dose from our institution. Overall survival (OS) and progression-free survival (PFS) were calculated from the first Lu-177 dose using the Kaplan–Meier method. Cox regression analysis was performed for PFS adjusted by grade, primary tumor site, metastasis sites (1 vs.≥ 2), presence of liver metastasis, and previous local or other systemic treatments. Krenning Score (KS) and the maximum standardized uptake value (SUVmax) were calculated from the pre-treatment Ga-68 PET/CT. Maximally Selected Rank Statistics (MSRS) test was used for SUVmax simple cutpoint estimate and PFS was calculated using the Kaplan–Meier method. Results: 36 pts were included; the median age was 51 (range: 33-80). 19 (52.8%) pts had primary pancreatic NET and 17 (47.2%) had non-pancreatic primary NETs. Tumor grading was classified based on Ki67%. 10 pts were G1 (28.6%), 18 pts were G2 (51.4%), 7 pts were G3 (20%). 7 pts (19.4%) and 28 pts (77.7%) had KS 3 and 4, respectively. 125 cycles of Lu-177 were applied with 3.5 cycles per pts (mean; range: 1-6). 12 (33.3%) pts experienced grade 1 and 2 toxicity, mainly fatigue (n=4). No grade 3 or 4 toxicities were reported. 4 (11.1%) patients died (n=3 G3; n=1 G2) with median follow-up of 90.5 months (range: 16-122). 11 pts (30.6%) lost follow-up after Lu-177 treatment. 29 pts (80.5%) were eligible for OS. 24-month and 36-month survival rates were 92,7% (95% CI 73.7 - 98.1) and 86,9% (95% CI 63.5 - 95.7) respectively. The median OS was not reached for G1 and G2 tumors, and it was 30 months for G3 tumors (p=0.001). 34 (94%) pts were eligible for PFS. The median PFS was 23 months (95% CI 30.5-64.9) for the entire cohort. The median PFS was 30 months for G1, 27 months for G2 pts, and 7 months for G3 pts. G1/G2 vs. G3 median PFS was statistically different in the uni- and multivariate analysis [HR 8.41 (95%CI 2.2-31.0; p=0.001)]. The primary site, metastasis sites, number of previous systemic treatments, previous local treatment, and presence of liver metastasis did not correlate with PFS in the multivariate analyses. Pts with SUVmax &gt; 34.53 exhibited a statistical trend toward a longer PFS (median 52.0 vs 18.7 months; p=0.06). Conclusions: This real-life study supports that Lu-177 provides long-term PFS in pts KS 3/4 with G1/G2 GEP-NETs independent of clinical characteristics and primary site. Although G3 pts have worse survival, selected G3 GEP-NETs may experience long OS after Lu-177 treatment. SUVmax values from the pre-treatment Ga-68 PET/CT study may select ideal pts for Lu-177.